Introduction of bubble CPAP in a teaching hospital in Malawi.

BACKGROUND: Continuous positive airway pressure (CPAP) is relatively inexpensive and can be easily taught; it therefore has the potential to be the optimal respiratory support device for neonates in developing countries. OBJECTIVE: The possibility of implementing bubble CPAP in a teaching hospital with a large neonatology unit but very limited resources was investigated. METHODS: A CPAP system was developed consisting of a compressor, oxygen concentrator, water bottle to control the pressure and binasal prongs. Neonates with birthweights between 1 and 2·5 kg with persistent respiratory distress 4 hours after birth were eligible for bubble CPAP. RESULTS: In the 7-week introduction period from 11 March until 27 April 2008, 11 neonates were treated with CPAP. Five of these neonates met the inclusion criteria and six neonates did not meet these criteria. Of the five neonates who received CPAP and met the inclusion criteria, three survived. The six infants who did not meet the inclusion criteria included three preterm infants with apnoea (all died), two with birthweights <1 kg (both died) and a firstborn twin (1.2 kg) who survived. No major complications of CPAP occurred. Bubble CPAP could be used independently by nurses after a short training period. CONCLUSION: Successful long-term implementation of CPAP depends on the availability of sufficient trained nursing staff.

Organic solvents increase membrane fluidity and affect bile flow and K+ transport in rat liver.

Following the earlier observation that inhalation of volatile lipid solvents and of narcotic gases causes cholestasis, we studied the effects of various organic solvents on bile flow, plasma membrane fluidity and potassium movement in rat liver. Both in vivo and in the isolated perfused liver, applications of CCl4, CHCl3, dichloromethane, trichloroethylene, halothane, benzene and cyclohexane elicited rapid and sustained but reversible cholestasis. A transient phase of choleresis was observed prior to and after cholestasis, during the increase and fall in liver tissue solvent concentrations, respectively. Tissue concentrations required to produce cholestasis were lower the higher the lipophilicity of the solvent. Membrane fluidity was measured in isolated basolateral liver cell membranes by fluorescence polarization. Fluidity increased with increasing solvent concentration, the increase being associated with either biphasic stimulation and inhibition of membrane enzymes (Na+,K(+)-ATPase, 5'nucleotidase) or with inhibition alone (Mg(2+)-ATPase). In the isolated perfused liver, application of organic solvents caused hepatic uptake of K+ that was followed by K+ release upon withdrawal of the solvent. The magnitude of K+ uptake elicited by the solvent was comparable with the effect of blocking K+ channels with 2 mM Ba2+, but Ba2+ was ineffective in the presence of the solvent. In contrast, application of ouabain caused K+ release in equal amounts in the absence and presence of the solvent, indicating that K+ uptake elicited by the solvent results from inhibition of K+ efflux through K+ channels rather than stimulation of the Na+,K+ pump. The data show that cholestasis elicited by lipid solvents is associated with an increase in membrane fluidity and with disturbance of liver K+ homeostasis. The significance of these observations is discussed with respect to other models of experimental cholestasis.

Prediction of the response to chemotherapy in acute leukemia by a short-term test in vitro.

To detect sensitivity or resistance of leukemic cells to chemotherapy prior to treatment, a short-term incubation method was employed. Blast cells from the peripheral blood or bone marrow of adult patients presenting with different forms of acute leukemia were analyzed for in vitro responsiveness to anticancer drugs in terms of suppression of 3H-uridine incorporation into cellular nucleic acids. The following agents were tested over a wide range of concentrations: Adriamycin, cytosine arabinoside, thioguanine, 6-mercaptopurine, prednisone, and 4-hydroperoxycyclophosphamide. Retrospectively, the in vitro data were compared to the clinical response of the patients to polychemotherapy. In the majority of the patients, in vitro cytotoxic effectiveness of Adriamycin (doxorubicin) and cytosine arabinoside reflected the in vivo situation. The levels of in vitro inhibition that could distinguish between drug-sensitive and drug-resistant diseases appeared to be 30% for Adriamycin and 20% for cytosine arabinoside. No correlation was found between the Adriamycin effect in vitro and the proliferative state (rate of 3H-thymidine incorporation) of the leukemic cell population. Serial in vitro sensitivity testing during the course of disease of various patients proved the ability of the test system to detect acquired resistance to chemotherapeutic agents. Therefore, the assay might serve as a reliable tool in the selection of effective chemotherapy in individual patients suffering from acute leukemia.

Different types of endotoxin-induced release of colony stimulating factors by adherent leucocytes in the presence of fresh and heat-inactivated autologous serum.

Human adherent leucocytes stimulate in vitro granulopoiesis by releasing colony stimulating factors (CSF), which promote the growth of myeloid committed stem cells (CFUC). The effect of lipopolysaccharide (LPS) on CSF generation by adherent leucocytes was studied with fresh and heat-inactivated autologous serum. Adherent leucocyte conditioned media were fractionated on Sephadex G-75. LPS, in the presence of fresh serum, caused a significant increase of CSF release by adherent leucocytes within 1 h. Heat inactivation of autologous serum abolished this effect. Adherent leucocyte CSF had 3 activity peaks at greater than 75 000, 23 000 and less than 4 000 daltons. LPS-fresh serum initiated CSF, harvested after culture periods of 1 and 24 h, disclosed identical elution profiles.

Proliferation kinetics and cyclic AMP as prognostic factors in adult acute leukemia.

In 41 adult patients with acute leukemia (myeloblastic, lymphoblastic, and undifferentiated), proliferation kinetics (as determined by double-label autoradiography) and cyclic adenosine 3',5'-monophosphate (cAMP) concentration were studied for their significance in the prediction of responsiveness to cytostatic therapy. Patients with good clinical response had significantly shorter turnover times and higher labeling indices in the bone marrow than did those who failed to respond to treatment. Cases for which cell kinetics did not correlate with clinical response were explained by variance in the distribution of leukemic blasts between the proliferative cell cycle and the resting pool. Good clinical response was also found to be associated with low levels of cAMP in leukemic cells prior to therapy, whereas high cAMP contents predicted failure. Low cAMP concentrations, however, did not necessarily correlate with short turnover times and vice versa. This might be due to fluctuations of the cAMP concentrations during the cell cycle.

Endotoxin-induced colony stimulating activity in normal and myeloid leukaemic subjects.

Low doses of endotoxin were administered to normal and acute anc chronic myeloid leukaemic subjects. Temperature, leucocyte count, blood colony stimulating activity and the number of circulating colony forming units were monitored. All subjects acquired fever while the leucocyte count remained unaltered. Blood CSA rose sharply in 6 normal individuals, but failed to increase in 4 acute leukaemic patients and in 2 patients with CML in blast crisis. 2 patients with CML in the chronic stage increased their blood CSA comparable to normal individuals. The number of circulating colony forming units rose following endotoxin with a peak at 30 min and declined subsequently. 4 patients with acute leukaemia showed no increase of circulating colony formers.

[Prognostic significance of the cyclic AMP concentration in acute leukemias]. / Prognostische Bedeutung der Konzentration von zyklischem AMP bei akuten Leukämien.

In patients with acute leukemia (myeloblastic, lymphoblastic, undifferentiated) proliferation kinetics and cyclic adenosine-3', 5'-monophosphate (cAMP) concentration of the leukemic cells were studied for their significance in the prediction of responsiveness to cytostatic therapy. Patients with good clinical response had significantly faster turnover and lower cAMP-levels than those who failed to respond to treatment.

Action of humoral factors derived from acute and chronic myeloid leukemic cells on in vitro myelopoiesis.

The experiments described in this paper were performed in order to elucidate a possible regulatory role of acute and chronic myeloid leukemic leucocytes. The influence of these cells on either activated or non-activated mouse bone marrow cells was measured, and the results were compared with the action of the two major leucocyte fractions, mononuclear cells and granulocytes. It was demonstrated that acute leukemic blasts were almost completely unable to activate myeloid committed stem cells (Colony Forming Units, CFUC). In contrast, blasts from patients with chronic myeloid leukemia (CML) in blastic crisis disclosed a variable pattern of activation, in that two out of three cases exerted normal stimulatory capacity. A possible inhibitory action of leukemic cells was the subject of further experiments. Acute leukemic blasts in some cases disclosed inhibitory activity, a few cases appeared to be without influence on normal proliferating CFUC. Granulocytes from patients with CML in the chronic phase showed inhibitory capacity when compared with granulocytes from normal individuals. It is apparent from these experiments that leukemic cells themselves may contribute to the regulatory derangements of leukemias.

Intermittent meningitic reaction with severe basophilia and eosinophilia in CNS leukaemia.

Light- and electron-microscope studies were performed on CSF cells from a patient with CNS leukaemia presenting with an intermittent meningitic reaction. Numerous fully matured basophilic and eosinophilic granulocytes with excess glycogen content accompained undifferentiated leukaemic blast cells in the CSF. Such a CSF cell reaction has not been previously reported. It is suggested that this isolated CSF reaction represents a special type of immediate hypersensitivity reaction triggered by an abnormal leukaemic giant cell clone, and mitigated by the accompanying eosinophilic granulocytes.

Production and diagnostic application of anti-human T-cell antisera.

This paper is intended to demonstrate the extension of experimental procedures used for the production of anti-chicken T-cell sera to the manufacturing of anti-human T-cell sera. Specific anti-chicken bursa (ABS) and anti-chicken thymus cell sera (ATS) were prepared in turkeys. The in vitro specificity of these sera was assessed by means of immunofluorescence and lymphocytotoxicity tests. The selective immunosuppressive effect of ABS was demonstrated in Obese strain (OS) chickens with spontaneous autoimmune thyroiditis, that of ATS in a skin allograft system. A specific anti-human T-cell serum was prepared by immunizing a horse with fetal human thymus cells. After appropriate exhaustive absorptions this serum was found to react specifically with human T-cells. An anti-T cell globulin (ATG) fraction prepared from the absorbed antiserum was then labelled with FITC for use in direct immunofluorescence tests. The potential diagnostic value of T-cell specific antibodies is discussed.